This project seeks basic information about the synthesis, structure and function of antihemophilic factor (AHF, factor VIII). The recent application of immunologic techniques to the study of this coagulation protein has led to significant progress in our understanding of AHF and of the hereditary bleeding disorders in which AHF activity is deficient, hemophilia A and von Willebrand's disease. In this project, more specific immunoassay methods will be developed to detect and quantify that region of the AHF molecule which is responsible for procoagulant function so that the relationship of the several properties of AHF (procoagulant activity, von Willebrand's factor activity, and precipitating antigens identified by rabbit anti-AHF) can be defined with greater precision. A combination of biochemical and immunologic methods will then be used to study the structure and function of normal AHF, with special emphasis on studies of subunits prepared from this very large glycoprotein and on the relationship of carbohydrate to biologic and immunologic properties. Parallel studies of the nonfunctional AHF-like protein which is present in plasmas from patients with hemophilia A will be directed toward an understanding of the specific molecular defect in this disease. Complementary studies of AHF synthesis and its physiologic control will also be undertaken.